发明名称 Molecules that selectively inhibit histone deacetylase 6 relative to histone deacetylase 1
摘要 This invention provides a compound having the structure:;whereinR1 is H, halogen, —NR5R6, —NR5—C(═O)—R6, —NH—C(═O)—OR7, —OR7, —NO2, —CN, —SR7, —SO2R7, —CO2R7, CF3, —SOR7, —POR7, —C(═S)R7, —C(═O)—NR5R6, —CH2—C(═O)—NR5R6, —C(═NR5)R6, —P(═O)(OR5)(OR6), —P(OR5)(OR6), —C(═S)R7, C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, aryl, heteroaryl, or heterocyclyl, wherein R5, R6, and R7 and are each, independently, H, C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;m is an integer from 0 to 2;R2 and R3 are each, independently, H, halogen, —NH2, —CX3, —C(═O)OR8, C(═O)R8, —C(═O)NR9R10, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, heteroalkyl, aryl, heteroaryl, or heterocyclyl; whereinX is Cl, Br, or F;R8, R9 and R10 are each, independently, H, C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;Q is —Ar1—Z— or —Z—Ar1—Z—, wherein Ar1 is aryl or heteroaryl; andeach occurrence of Z is independently present or absent, and when present is —O—, —S—, —CH2—, —C(O)——NH—, —NH—NH—, —NHC(═O)—, —C(═O)NH—, —NHC(═O)CH2NH—,—NHC(═O)CH2C(═O)—, —N(OH)—, —CH2CH2— or—NHC(═O)CH═CH—; andR4 is alkyl, —OR11 or —NH—OR11, wherein R11 is H, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, aryl, heteroaryl, or heterocyclyl, andwhen Q is —Ar1—Z—, Z is absent, Ar1 is phenyl, R2 and R3 are H, n=1, and R4 is —NHOH, then R1 is other than carbazole, tetrahydro-β-carboline, tetrahydro-γ-carboline, —C(═O)—NR5R6 and —NR5—C(═O)—R6, wherein one of R5 or R6 is quinoline and the other of R5 or R6 is H; or a pharmaceutically acceptable salt thereof.
申请公布号 US9499479(B2) 申请公布日期 2016.11.22
申请号 US201214349291 申请日期 2012.10.03
申请人 THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK;SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH 发明人 Breslow Ronald;Marks Paul A.
分类号 C07C25/10;C07C259/08;C07C259/10;C07D215/40;C07D235/06;C07D209/08;C07D209/18;C07C259/06;C07C275/64;C07D209/24;C07D209/42;C07D215/06 主分类号 C07C25/10
代理机构 Cooper & Dunham LLP 代理人 White John P.;Cooper & Dunham LLP
主权项 1. A compound having the structure: wherein R1 is —NR5—C(═O)—R6 or —C(═O)—NR5R6, whereinR5 is R6 is whereinX is a Cl, Br, or F; andR12 is H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; m is an integer from 0 to 2; R2 and R3 are each, independently, H, halogen, —NH2, —CX3, —C(═O)OR8, C(═O)R8, —C(═O)NR9R10, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, heteroalkyl, aryl, heteroaryl, or heterocyclyl; whereinX is Cl, Br, or F;R8, R9 and R10 are each, independently, H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; Q is —Ar1—Z— or —Z—Ar1—Z—, wherein Ar1 is wherein X is a Cl, Br, or F; andeach Z is absent; and R4 is alkyl, —OR11 or —NH—OR11, wherein R11 is H, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, aryl, heteroaryl, or heterocyclyl,or a pharmaceutically acceptable salt thereof.
地址 New York NY US